Mechanism of Suoquanwan on Enuresis Based on Network Pharmacology and Experimental Verification / 中国实验方剂学杂志

Objective:To explore the targets and relevant signaling pathways of Suoquanwan in the treatment of enuresis using network pharmacology，and animal expriments are applied to further define its mechanism of action. Method:Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） database was used to screen out active chemical components of Suoquanwan，varieties of systematic biological databases were integrated to construct the "active component-disease-target" network relationship，and the common protein protein interaction network（PPI） network genes were functionally enriched. Quantitative real time polymerase chain reaction（Real-time PCR） and Western blot were used to verify the effect of Suoquanwan on AVPR2 and DRD2 gene. Result:A total of 32 active ingredients were screened from Suoquanwan. These active ingredients were interacted with 131 potential targets relating to Enuresis，which contained 14 core target genes，namely arginine vasopressin receptor 2 （AVPR2）， neurotrophic receptor tyrosine kinase 1（NTRK1）， dopamine receptor D2（DRD2）， opioid receptor mu 1（OPRM1）， 5-hydroxytryptamine receptor 1A（HTR1A）， 5-hydroxytryptamine receptor 1B（HTR1B），solute carrier family 6 member 4（SLC6A4），Adrenoceptor Alpha 2A（ADRA2A）， prostaglandin-endoperoxide synthase 2（PTGS2）， cholinergic receptor muscarinic 2（CHRM2）， solute carrier family 6 member 3 （SLC6A3）， 5-hydroxytryptamine receptor 6（HTR6）， solute carrier family 6 member 2（SLC6A2）， cytochrome P450 family 2 subfamily C member 19（CYP2C19）. Gene enrichments mainly involved to G protein-coupled receptor signaling pathway，regulation of trans-synaptic signaling，regulation of neurotransmitter transport and neuroactive ligand-receptor interaction. Real-time PCR and Western blot results showed that Suoquanwan could enhance the expression of AVPR2 in rat kidney，and weaken the expression of DRD2 in rat adrenal. Conclusion:The main chemical constituents in Suoquanwan may alleviate enuresis by regulating AVPR2 and DRD2 and then participating in the G protein-coupled receptor signaling pathway，regulation of trans-synaptic signaling，regulation of neurotransmitter transport and other biological processes.

The predictive analysis of action mechanism for classic TCM excellent prescriptions of Danggui Buxue decoction on diabetes with TCMIP / 中国药理学通报

To explore the pharmacodynamic material basis and mechanism of the classic TCM excellent prescriptions(cTCMep) Danggui Buxue decoction, so as to provide more choices for the prevention and treatment of diabetes mellitus (DM). Methods With the integrative pharmacology of traditional Chinese medicine (TCMIP) , we predicted the pharmacodynamic material basis and mechanisms of the cTCMep Danggui Buxue decoction for treatment of DM. Results The 50 " Astragalus-Angelica" components in the cTCMep Danggui Buxue decoction directly or indirectly acted on 60 key drug targets. These drug targets restored the disease imbalance network of DM and its complications by acting on 30 major regulatory pathways such as nervous-endocrine system, gap junction, hormone signaling pathways, and cardiovascular circulatory system. The main components of Astragalus membranaceus membranaceus involved in the prevention and treatment of DM were astragalosides, astragalosides and alavonoids. The main components involved in the prevention and treatment of DM in Angelica sinensis were organic acids such as ferulic acid, oil components such as (3-sweet myrrh, stigmasterol-|3-D-glucoside, smbelliferol and scopolamine. Conclusions The 50 " Astragalus-Angelica" components in the cTCMep Danggui Buxue decoction may play a role in preventing and treating DM through the AVPR1A, AVPR1B and AVPR2 (AVPR: Arginine vasopressin receptor, three subtypes), of which Astragalus membranaceu is the key component.

Preliminary observation of efficacy and safety of arginine vasopressin receptor antagonist in the treatment of syndrome of inappropriate secretion of antidiuretic hormone / 中国医师进修杂志

Objective To observe the efficacy and safety of arginine vasopressin receptor antagonist tolvaptan for treating hyponatremia caused by syndrome of inappropriate secretion of antidiuretic hormone (SIADH).Methods Six patients diagnosed with SIADH were enrolled in this study.Four cases were allocated to tolvaptan group (oral tolvaptan 15-60 mg/d,the dosage was adjusted based on the level of serum sodium).Two cases were allocated to regular treatment group (liquid was limited 1 000 ml/d,intravenous drip was less than 3％ sodium chloride and/or oral salt capsule 10-15 g/d several times was adjusted based on the level of serum sodium).Data of the level of serum sodium at 4,7 d,baseline value of serum sodium,serum sodium at the first normal time,24 h urine and weight change were collected.Safety assessment was given before and after treatment,including medical history,physical examination,electrocardiogram,laboratory tests,and incidence of adverse events.Results The level of serum sodium in tolvaptan group increased from the first day of the treatment.During the period of treatment,serum sodium at 4 d increased 22,16,14,11 mmol/L compared with the baseline value respectively.No obvious change of sodium was observed in regular treatment group compared with the baseline value.For 7 d treatment,serum sodium level increased 14,13,14,13 mmol/L in tolvaptan group compared with the baseline level respectively.Only 2 cases in regular treatment group increased 4 mmol/L,and sodium level in regular treatment group did not reach the lower limit of normal level of serum sodium.In tolvaptan group,all patients urine output increased after 1 d treatment and began to stabilize in 3 d.24 h urine putouts were much more than 1 500 ml during treatment.Urine putouts 780-1 400 ml were observed in regular treatment group.There was no difference before and after treatment.Although weight dropped after treatment in the two groups,weight in tolvaptan group fell obviously.In the two groups,there was no difference in blood pressure and heart rate before and after treatment.There were no serious complications and adverse events.Conclusions Compare with regular treatment,arginine vasopressin receptor antagonist is more effective therapy because it can correct the SIADH in patients with hyponatremia and reduce water retention.It also has a good security.

A case of congenital nephrogenic diabetes insipidus: his pedigree and clinical evaluation / 中华内分泌代谢杂志

A case of arginine vasopressin receptor 2 ( AV PR2 ) mutation in a boy with congenital nephrogenic diabetes insipidus was reported.Genomic DNA of the boy and his family members was extracted.The entire coding region of the AVPR2 gene were amplified by PCR.The amplified products were purified and sequenced.The results were compared with the normal one of the gene bank.The impact of the mutation on AVPR2 structure was discussed with respect to homology structure model.The analysis identified a T to G transition in exon 2 of the AVPR2 gene,resulting in substitution of leucine for arginine at amino acid residue 168.Furthermore,the patient′s mother and sister were heterozygous for this mutation,and the father was normol.

A Case of Congenital Partial Nephrogenic Diabetes Insipidus

The most common form of genetic nephrogenic diabetes insipidus(NDI), a rare inherited disorder, is congenital and is transmitted in an X-linked recessive mode. It is refractory to the antidiuretic effect of normal to moderately increased levels of plasma arginine vasopressin(AVP) but, in some cases, may respond to high levels of the hormone or its analogue, deamino-D-arginine vasopressin(DDAVP). X-linked congenital NDI has now been linked to over 128 different mutations in diverse coding regions of the AVP receptor 2(AVPR2) gene. The functional effects of these mutations vary from complete loss of responsiveness to a simple shift to the right in the dose response curve. We report a case of congenital partial NDI, with transversion of A to G at codon 280 of the AVPR2 gene, resulting in a subsequent change of amino acid from tyrosine to cysteine, and that has been effective with hydrochlorothiazide and high dose of DDAVP.